The Science Core exists to provide reagents and services to the various projects within this Program Project grant, and to the Neuropathology and Animal Cores. The need for specific reagents and services are often common to multiple projets and cores, as they are for projects on other Program Project grants. The most efficient method of operation for providing reagents and service requiring complex, expensive equipment is therefore via a central core with highly skilled staff. For this renewal of the Program Project, the Science Core will purify prion protein (PrP) from infected rodent brains for structural studies in Project 2 , in addition to use as standards in Projects 1 and 3. It will also provide a variety recombinant Fabs and monoclonal anti- PrP antibodies, in addition to developing new anti-PrP antibodies with higher affinities. These reagents will be required in large quantities for Western blotting in projects 1, 2 and 3, immunohistochemistry by the Neuropthology core (Core C), and as specific binding controls in Project 4. Recombinant PrP will required for the screening assays in Project 3, in addition to its use as standrds in all other Projects. In addition, the Science Core will provide screening of transgenic mice from the Animal Core (Core D), particularly in support of Project for the production of novel mouse models to test the drugs developed in Projects 2 and 3. Lastly, quinacrine biodistribution studies for both human tissues from Project! and mouse tissue from Core D (in support of project 2), will be performed by the Science Core.